This proposal describes a retrospective, epidemiologic study to evaluate the role of hepatitis B surface antigen (HBsAg) as a risk factor in the development of primary hepatocellular carcinoma (PHC) in the United States. The major resource is a computerized record containing identifying information on approximately 20,000 blood donors found reactive for HBsAg over a 9-10 year period plus a comparable HBsAg nonreactive control population of similar size. The crude mortality of each group and the identity of those donors who have died will be determined with the cooperation of the Social Security Administration. Thereafter, appropriate vital statistics records will be accessed in order to determine the cause of death in each case. Meanwhile, the age and sex distribution of the index and control populations will be determined. The age- and sex-specific incidence of PHC will be estimated for cohorts. Calculations suggest that there may be as many as 100 cases of PHC in the index group and a maximum of 5 among controls. It is unlikely that HBsAg will be found to be a risk factor in any other cause of death with the possible exception of nonalcoholic cirrhosis, but the data will be analyzed for such trends. If, as a result of this study, excess mortality is documented among HBsAg-reactive donors, then a detailed protocol for a prospective study will be developed.